Multidisciplinary Study of Social Behavior and Emotion in Frontotemporal Dementia

描述(申请人提供)：额颞性痴呆(FTD)是一种与年龄相关的神经退行性疾病，以社会和道德行为障碍为特征。FTD是破译老年人社会行为的神经生物学基础的独特窗口。FTD的最早症状反映了自我参照的社会行为(例如，尴尬)、对他人的情感意识(例如，移情)和道德情感体验(例如，公平)的下降。这些行为变异型FTD患者也是不受约束的，无法规范自己的社会行为。这些干扰的共同潜在机制可能是驱动社会和道德行为的情绪受损(Fiske，2002；Olsson和Ochsner，2008)。我们的工作表明，社会环境改变了自主情绪反应(Gehricke和Shapiro，2001)，并且右脑负责这些反应(Spence等人，1996)和bvFTD中主要的区域性脑萎缩(McMurray等人，2006；Mendez等人，2008a)。总之，这些研究表明，特定的右额颞区在特定的社会道德情绪(SME)中起着特定的中介作用。为了这一应用，一个由社会科学家和神经学家组成的多学科团队聚集在一起，研究bvFTD中的SME。这个团队在自然主义的环境中观察最明显的社会道德行为，为bvFTD构建一个“人种图”或行为词典，用行为和心理生理学方法对其进行测试，并用皮质映射技术调查涉及的大脑区域。该应用程序将定义bvFTD患者与阿尔茨海默病(AD)患者和正常对照组相比的SME及其障碍。它将招募33名早期bvFTD患者，并在三个特定目标上将他们与33名AD患者和33名正常对照组进行比较。具体目标1将评估由飞行员数据生成的预测伦理图。这一具体目标将应用人种学方法来观察患者在家中的互动，对话分析以了解他们的言语互动，以及补充的行为实验和量表。在具体目标2中，应用程序将进一步使用心理生理测量来评估这些行为的特异性。对于这两个特定的目标，这一应用程序预测与对照组相比，bvFTD患者的社会道德情绪行为会受到更大和更具体的干扰。在具体目标3中，这项应用将把SME的评估与磁共振成像(MRI)上的区域异常和三维皮质映射联系起来。这项应用预测，大多数SME障碍将与右额叶腹内侧区的萎缩相关，而去抑制和调节障碍对应于右侧眶前-前颞区。这项创新的神经成像可能会揭示其他特定的大脑行为定位。最终，这一应用可以阐明衰老的神经退行性疾病如何影响社会和道德行为，并可以极大地促进我们对社会行为神经科学的理解。 公共卫生相关性：许多精神或大脑疾病在社会行为或人际互动方面存在障碍。这一应用程序结合了许多专家来研究额颞部痴呆患者的精神障碍社交行为。该项目的结果可以阐明精神障碍或大脑疾病是如何改变社会行为的。

DESCRIPTION (provided by applicant): Frontotemporal dementia (FTD) is an age-related neurodegenerative disorder characterized by disturbances in social and moral behavior. FTD is a singularly unique window to deciphering the neurobiological basis of social behavior in older age. The earliest symptoms of FTD reflect declines in self-referential social behavior (e.g., embarrassment), in emotional awareness of others (e.g., empathy), and in moral emotional experiences (e.g., fairness). These behavioral variant FTD patients are also disinhibited and unable to regulate their social behavior. The common, underlying mechanism for these disturbances may be impairment in the emotions that drive social and moral behavior (Fiske, 2002; Olsson and Ochsner, 2008). Our work has shown that social context alters autonomic emotional responses (Gehricke and Shapiro, 2001) and that the right hemisphere is responsible for both these responses (Spence et al, 1996) and the predominant regional brain atrophy in bvFTD (McMurtray et al, 2006; Mendez et al, 2008a). Together, these studies suggest that specific right frontotemporal regions mediate in specific in sociomoral emotions (SME). For this application, a multidisciplinary team of social scientists and neuroscientists have come together to study SME in bvFTD. This team takes observations of sociomoral behavior in a naturalistic setting, where it is most evident, constructs an "Ethogram" or behavioral dictionary for bvFTD, tests it with behavioral and psychophysiologic measures, and investigates the brain regions involved with cortical mapping techniques. This application will define the SME and their disturbances in patients with bvFTD, compared to patients with Alzheimer's disease (AD) and normal controls. It will recruit 33 patients with early bvFTD and compare them to33 patients with AD and 33 normal controls on three Specific Aims. Specific Aim 1 will evaluate the predicted Ethogram, generated by pilot data. This Specific Aim will apply ethnographic methods for participant observation of patient interactions in their homes, conversational analysis to understand their verbal interactions, and supplemental behavior experiments and scales. In Specific Aim 2, the application will further evaluate the specificity of these behaviors with psychophysiologic measures. For these two Specific Aims, this application predicts greater and more specific disturbances in sociomoral emotional behaviors among patients bvFTD, in comparison to controls. In Specific Aim 3, this application will correlate the assessments of SME with regional abnormalities and three-dimensional cortical mapping on magnetic resonance imaging (MRI). This application predicts that most SME disturbances will correlate with atrophy in the right ventromedial frontal regions, whereas disinhibition and dysregulation corresponds to right orbitofrontal-anterior temporal regions. Other specific brain-behavior localizations may be revealed by this innovate neuroimaging. Ultimately, this application can elucidate how neurodegenerative diseases of aging impact social and moral behavior and can greatly accelerate our understanding of the neuroscience of social behavior. PUBLIC HEALTH RELEVANCE: Many mental or brain disorders have disturbances in social behavior or interpersonal interactions. This application combines many specialists to study disturbed social behavior in frontotemporal dementia. The results of the project can clarify how social behavior is altered by mental disorders or brain diseases.